I. Problem/Condition.

Sexually acquired disease (also referred to as sexually transmitted infections [STIs] or previously sexually transmitted diseases [STDs]) is comprised of various infections. Given that there are many infections, the signs and symptoms are broad but often related to both the male and female genitourinary systems.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The differential should be based on the symptoms presented. Common symptoms include:

A. Be professional, non-judgmental, confidential, and comfortable in discussing details of sexual behaviour and history.

B. Take the history when the patient is fully clothed and avoid lengthy discussion during patient physical examination.

C. Use open ended questions, make no assumptions regarding gender of partners, gender role or sexual behaviors.

D. Be an active listener, show empathy.

2. After obtaining a sexual history the following should also be gathered: past medical and social history, immunizations, history of STD testing along with current and past symptoms. Time of onset, characterization of signs and symptoms, alleviating and aggravating factors should be elicited. The patient should be asked about self- perceived physical exam changes, i.e., rashes, discharge, swelling, etc.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

The physical exam should be based on the gathered history; however, it is important to be mindful that sometimes certain signs and symptoms are not disclosed given the privacy and stigmata that come along with getting a diagnosis of a STI. A thorough and complete exam should be taken, paying closer attention to the skin, lymphatic system, musculoskeletal system, and most importantly, the genitourinary system.

Vaginal pelvic exam

Penile/scrotal exam

Skin survey/exam including pubic hair

Oral exam

Lymph node exam

Gastrointestinal and musculoskeletal exam

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Testing for specific STDs depends on risk factors. Testing may include may include:

C. Diagnostic criteria for sexually acquired diseases

1. HIV - having other STDs increases the risk of acquiring HIV. It starts as a brief acute viral syndrome (although many are asymptomatic) but eventually transitions to a chronic illness. It is important to diagnose early, to prevent both sequelae and further transmission, as HIV is highly infectious in the acute stage. Diagnosis is tricky since HIV antibodies are often negative early. Testing starts with screening with serology (antigen/antibody or antibody immunoassay). Keep in mind that rapid tests become reactive later than the other serologic markers. Once a positive test occurs, it is followed by a confirmatory test (antibody differentiation assay, western blot or indirect immunofluorescence). Given that there might be discordance in early infection, HIV RNA testing can also be performed. Testing for hepatitis B and hepatitis C is imperative prior to initiation of antiretroviral therapy (ART) as co-infection will likely change choice of ART.

2. Chlamydia - the most commonly reported bacterial STD in the US is frequently asymptomatic. In women, it can cause pelvic inflammatory disease, infertility, ectopic pregnancy and chronic pelvic pain. In males, it is mostly asymptomatic, but may result in urethral discharge. It can also cause proctitis and conjunctivitis. Diagnosis is made by first catch urine or vaginal samplesent for NAAT.

3. Gonorrhea - the second most commonly reported STI causes cervicitis, urethritis and proctitis. Diagnosis is made by testing body fluids (endocervical, urethral, vaginal swabs and urine) using NAAT. Culture can be used in the setting of rectal, oropharyngeal and conjunctival specimens.

5. Syphilis - caused by spirochete bacteria Treponema pallidum and is characterized by 3 progressive stages. Diagnosis can be established by reactive syphilis serology and clinical findings. Serology usually begins with nontreponemal testing (VDRL and RPR) that is nonspecific. If these are positive, confirmatory treponemal testing is pursued looking for antibodies (FTA-ABS, TP-PA, EIAs, etc). Some labs employ the “reverse algorithm” with initial treponemal testing confirmed by nontreponemal testing. This is because treponemal antibodies occur earlier than nontreponemal. The most definitive diagnostic method is to look for motile spirochete via darkfield microscopy of exudative fluid from lesions.

Secondary syphilis- most characteristic features include maculopapular rash of palms and soles, lymphadenopathy, fever, fatigue and malaise typically appearing weeks to months after onset of primary stage. Other sequelae include: hepatitis, septic meningitis and glomerulonephritis.

Latent syphilis - infection is confirmed by reactive serology in the absence of clinical findings. Early latent is defined as duration <1 year and late latent is defined as >1 year. However, it is very common to have syphilis of unknown duration.

6. Chancroid - characterized by one or more painful genital ulcers and tender suppurative inguinal adenopathy caused by Haemophilus ducreyi. Diagnosis is usually made based by physical examination, in addition to ruling out herpes simplex virus and through laboratory testing of serum or ulcer exudate. A definitive diagnosis of chancroid is difficult to establish in the laboratory because H. ducreyi on special culture media is hard to isolate (sensitivity is <80%).

7. Lymphogranuloma Venereum (LGV) - caused by C. trachomatis. It presents as tender inguinal and/or femoral lymphadenopathy that is typically unilateral. There can also sometimes be a genital ulcer or papule at site of inoculation. Rectal exposure in women or MSM can result in proctocolitis, manifested as rectal/anal pain, constipation, fever, and/or tenesmus. Untreated, this can lead to chronic, colorectal fistulas, strictures and secondary bacterial infections. Diagnosis is made based on clinical suspicion, C. trachomatis testing (culture, direct immunofluorescence or NAAT), and the exclusion of other STIs.

8. Pubic lice (Phthirus pubis) - typically found attached to hair in the pubic area but sometimes are found on coarse hair elsewhere (e.g., eyebrows, eyelashes, beard, chest, armpits). Infestations are characterized by itching.

9. Anogenital warts - caused by human papilloma virus (HPV), most commonly serotypes 6 or 11. Genital warts are usually asymptomatic, flat, papular, or pedunculated growths on the genital mucosa or at the anogenital tract. Diagnosis is usually made by visual inspection and confirmed by biopsy. HPV vaccine against the cancer causing subtypes is available.

11. Trichomoniasis - most prevalent non-viral STD in the US. The majority of patients are asymptomatic, but women can have yellow-green, malodorous vaginal discharge while men can present with urethritis, epididymitis, or prostatitis. Diagnostic testing only indicated if vaginal discharge present.

A. Management of sexually acquired diseases.

1. Control of Symptoms

Severe pain of lesions can be controlled by narcotic analgesics or NSAIDS. Itching can be relieved by oral antihistamines.

2. Treatment of infection

1. HIV - Antiretrovirals should be started in acute HIV infection. Guidelines have also changed in those with chronic infection so that now, regardless of CD4 count, ART is recommended. Resistance testing should be performed to tailor regimens. Initial regimen usually includes two nucleoside reverse transcriptase inhibitors with combination of a third drug (integrase strand transfer inhibitor or non-nucleoside reverse transcriptase inhibitor or protease inhibitor with a pharmacokinetic enhancer). Additionally, it is important to screen for hepatitis B and hepatitis C which might change ART regimens.

2. Chlamydia - Azithromycin 1g orally in a single dose or Doxycycline 100 mg orally twice a day for 7 days. Alternatives: Erythromycin base 500 mg orally four times a day for 7 days/levofloxacin 500 mg orally daily for 7 days.

3. Gonorrhea - Ceftriaxone 250 mg IM in a single dose or Cefixime 400 mg orally single dose + Azithromycin 1g orally (due to likely co-infection with Chlamydia). Alternative: spectinomycin 2g IM in a single dose. Fluoroquinolones are NOT recommended due to resistance.

4. HSV genital herpes - antiviral therapy can be helpful for symptom management, however, it is not curative. According to the Centers for Disease Control and Prevention (CDC) STD treatment guidelines:

First clinical episode (7-10 days of therapy, with option to extend after 10 days if healing is incomplete: Acyclovir 400 mg orally three times a day for 7-10 days or Acyclovir 200 mg orally five times a day for 7-10 days or valacycovir 1 gram orally twice a day for 7-10 days or famciclovir 250 mg orally three times a day for 7-10 days

Suppressive therapy: Acyclovir 400 mg orally twice a day or valacyclovir 1 gram orally once a day or famciclovir 250 mg orally twice a day (valacyclovir 500 mg once a day is another option, but might be less effective than other valacyclovir or acyclovir dosing if >10 episodes per year)

Episodic therapy (start during prodrome or within 1 day of lesion onset): Acyclovir 400 mg orally three times a day for 5 days or 800 mg twice a day for 5 days or 800 mg three times a day for 2 days or valacyclovir 500 mg twice a day for 3 days or valacyclovir 1 gram orally once a day for 5 days or famciclovir 125 mg orally twice daily for 5 days or famcicovir 1 gram orally twice daily for 1 day or famciclovir 500 mg once followed by 250 mg twice daily for 2 days

Neurosyphilis - aqueous crystalline penicillin G 18-24 million units per day - given 3-4 million units IV every 4 hours or continuous infusion for 10-14 days. Alternatives: Procaine PCN 2.4 million units IM once daily + probenecid 500 mg orally four times a day - both for 10-14 days.

If patient also has HIV, PCN should be used as opposed to alternative regimens.

6. Chancroid - Azithromycin 1g orally in a single dose or ceftriaxone 250 mg intramuscularly (IM) in a single dose. Alternatives: Ciprofloxacin* 500 mg orally twice a day for 3 days or Erythromycin base 500 mg orally three times a day for 7 days.

7. LGV - Doxycycline 100 mg orally twice a day for 21 days. Alternative: Erythromycin base 500 mg orally four times a day for 21 days.

8. Pubic Lice - Permethrin 1% cream or Pyrethrins with piperonyl butoxide (both are meant to be applied and washed off after 10 minutes) Alternatives: Malathion 0.5% lotion (applied and washed off after 8-12 hrs).

10. Bacterial Vaginosis: Metronidazole 500 mg orally twice daily for 7 days or metronidazole gel 0.75%, one full applicator (5g) intravaginally once a day for 5 days or clindamycin cream 2%, one full applicator (5g) intravaginally at bedtime for 7 days.

3. Prevention of other STDs through counseling and education of patient and sex partner

Discuss the asymptomatic nature of many STDs and the need for screening, the relationship of STDs to HIV risk, the need for partner treatment if indicated, and partner notification communication. Additionally, talking about pre-exposure vaccinations, condoms and other barrier methods is advised. You may also identify social support, domestic violence, substance abuse and the need for social services or mental health referral.

Expedited Partner Treatment: You can also provide single-dose antibiotics to patients with chlamydia or gonorrhea for delivery to sexual partners from the past 60 days. Check with your state’s guidelines or the CDC to see if this is permissible.

Patients with non-viral STDs and their sex partners should abstain from sexual intercourse until seven days after initiating treatment.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

1. Advise about common reactions to antibiotics including oral thrush or yeast infections.

2. Always ask for any drug allergic reactions so that an alternative regimen may be prescribed.

3. Pregnancy/childbearing age women need to be identified, as some treatment regimens may be contraindicated.

"Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents". Department of Health and Human Services. http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.